Transient ischemic attack without self-awareness of symptoms witnessed by bystanders: analysis of the PROMISE-TIA registry.

BACKGROUND AND PURPOSE: A transient ischemic attack (TIA) can occur without self-awareness of symptoms. We aimed to investigate characteristics of patients with a tissue-based diagnosis of TIA but having no self-awareness of their symptoms and whose symptoms were witnessed by bystanders. METHODS: We used data from the multicenter registry of 1414 patients with a clinical diagnosis of TIA. For patients without evidence of ischemic lesions on imaging, clinical characteristics were compared between patients with and without self-awareness of their TIA symptoms. RESULTS: Among 896 patients (559 men, median age of 70 years), 59 (6.6%) were unaware of their TIA symptoms, but had those symptoms witnessed by bystanders. Patients without self-awareness of symptoms were older and more frequently female, and more likely to have previous history of stroke, premorbid disability, and atrial fibrillation, but less likely to have dyslipidemia than those with self-awareness. Patients without self-awareness of symptoms arrive at hospitals earlier than those with self-awareness (P < 0.001). ABCD2 score was higher in patients without self-awareness of symptoms than those with self-awareness (median 5 vs. 4, P = 0.002). Having no self-awareness of symptoms was a significant predictor of ischemic stroke within 1 year after adjustment for sex, ABCD2 score, and onset to arrival time (hazard ratio = 2.44, 95% confidential interval: 1.10-4.83), but was not significant after further adjustment for arterial stenosis or occlusion. CONCLUSIONS: Patients with a TIA but having no self-awareness of their symptoms might have higher risk of subsequent ischemic stroke rather than those with self-awareness, suggesting urgent management is needed even if patients have no self-awareness of symptoms.

Inhibitory effects of Japanese apricot (Prunus mume Siebold et Zucc.; Ume) on Helicobacter pylori-related chronic gastritis.

OBJECTIVES: We investigated the correlation between Japanese apricot (JA) intake and Helicobacter pylori-related chronic atrophic gastritis (CAG). METHODS: A questionnaire was administered and serum anti-H. pylori IgG antibodies measured in 1358 asymptomatic adults. The subjects were divided into high-intake and low-intake groups. Histological and serological evaluation of H. pylori-related CAG was performed in 68 non-elderly volunteers. RESULTS: The H. pylori-negative rate did not differ significantly between the high-intake and low-intake groups. Mean antibody titers were lower in the high-intake group, but the difference was not significant. There was no significant difference in the rate of H. pylori infection on the basis of JA intake when subjects were stratified by age. Among H. pylori-positive non-elderly subjects, antibody titers were significantly lower in the high-intake group (P=0.041). Endoscopic tissue biopsy from the 68 volunteers showed less H. pylori bacterial load and mononuclear infiltration irrespective of gastric site in the high-intake group. In the high-intake group, antral neutrophil infiltration was significantly less pronounced and corporal atrophy was less extensive. Serological evaluation using serum PG levels also confirmed these histopathological data. CONCLUSIONS: Our findings strongly indicate a preventive effect of JA intake on CAG by inhibiting H. pylori infection and reducing active mucosal inflammation.

Human serum paraoxonase concentration predicts cardiovascular mortality in hemodialysis patients.

AIMS: Human serum paraoxonase (PON1) is associated with high-density lipoprotein, and inhibits oxidative modification of low-density lipoprotein. Therefore, PON1 is supposed to contribute to the prevention of atherosclerosis. We and other investigators have shown that the enzymatic activities and concentrations of PON1 were decreased in maintenance hemodialysis (HD) patients. However, the effect of PON1 status on the long-term outcome of HD patients has not been reported. In this study, we examined the association between baseline PON 1 status and cardiovascular mortality in an observation study of an outpatient HD population. PATIENTS AND METHODS: The relation between baseline cardiovascular risk factors and clinical events was investigated, during 6 years of follow-up, in 81 HD patients (50 males and 31 females) whose enzymatic activities, concentrations and genetic polymorphisms of PON1 had been determined in a previous study. RESULTS: During follow-up for 6 years, we recorded 42 deaths, including 24 fatal cardiovascular events. In univariate analyses, baseline PON1 concentration was associated with not only cardiovascular mortality (p < 0.005), but also all-cause mortality (p < 0.001) during the period of follow-up, as were age, preexisting cardiovascular disease (CVD) and hemoglobin concentration. In a multivariate Cox regression analysis, PON1 concentration retained significant associations with cardiovascular mortality (p < 0.05) and all-cause mortality (p < 0.005) even after correction of known risk factors for CVD or mortality in HD patients. Using Kaplan-Meier survival curves, we assessed the association between low and high concentrations of PON1 divided according to the median value (7.52 U/ml). Significantly increased cardiovascular mortality (log rank 6.125, p = 0.01) and all-cause mortality (log rank 7.113, p < 0.01) were detected in the patients with low PON1 concentrations. CONCLUSIONS: These data suggest that low PON 1 concentration may be an independent predictor of cardiovascular mortality in maintenance HD patients.

Emergence of non-random structure in local food webs generated from randomly structured regional webs.

Previous studies have shown that high-resolution, empirical food webs possess a non-random network structure, typically characterized by uniform or exponential degree distributions. However, the empirical food webs that have been investigated for their structural properties represent local communities that are only a subset of a larger pool of regionally coexisting species. Here, we use a simple model to investigate the effects of regional food web structure on local food webs that are assembled by two simple processes: random immigration of species from a source web (regional food web), and random extinction of species within the local web. The model shows that local webs with non-random degree distributions can arise from randomly structured source webs. A comparison of local webs assembled from randomly structured source webs with local webs assembled from source webs generated by the niche model shows that the former have higher species richness at equilibrium, but have a nonlinear response to changing extinction rates. These results imply that the network structure of regional food webs can play a significant role in the assembly and dynamics of local webs in natural ecosystems. With natural landscapes becoming increasingly fragmented, understanding such structure may be a necessary key to understanding the maintenance and stability of local species diversity.

Cerebral blood flow index image as a simple indicator for the fate of acute ischemic lesion.

BACKGROUND AND PURPOSE: To evaluate the feasibility of utilizing cerebral blood flow (CBF) index images, we attempted to investigate 1) whether CBF index images can reveal the resulting infracted area, 2) whether the CBF index can correlate other modality (SPECT). METHODS: DWI and DPI were obtained in 17 patients within 12 hours of stroke onset and follow up MRI. On three DPI delivered images, namely relative regional cerebral blood volume (rrCBV), uncorrected mean transit time (MTTu) and CBF index images, correlations between initial lesion volume of and follow up infarction volume of three images and rCBF images delivered with singular value decomposition (SVD) methods were assessed. Then 99mTc-ECD SPECT was taken immediately after MRI to correlate to MRI data. RESULTS: Among the three images, lesion volume of CBF index images against follow up infarct volume had the highest correlation (r = 0.995) to a linear fit and the slope was closest to 1.0 (0.91) and had identical accuracy to the regression coefficient of rCBF images. CBF index well correlated to SPECT delivered CBF. CONCLUSION: CBF index images can accurately predict final infarct volume. Evaluating CBF index images together with DWI can guide the initial assessment in the acute stage of cerebral ischemia.

Neuroprotective effect of immunosuppressant FK506 in transient focal ischemia in rat: therapeutic time window for FK506 in transient focal ischemia.

Tacrolimus (FK506), an immunosuppressant currently used in clinic, is known to have neuroprotective properties. However, effects in focal ischemia are shown only in a endothelin induced middle cerebral artery (MCA) occlusion model or with filament technique at a relatively high dose. We have previously shown that FK506 had significant protective effects at a low dose of 0.3 mg kg(-1) when administered immediately after ischemia. In this study, we explored the therapeutic time window of FK506 at this low dose, in a transient focal ischemia model using filament technique. Male Sprague-Dawley rats were subjected to 2 h MCA occlusion and subsequent reperfusion. They received FK506 or vehicle (0.3 mg kg(-1)) i.v. at 30, 60 or 120 min after induction of ischemia, and were decapitated 24 h after ischemia. FK506 injected at 30 and 60 min significantly reduced cortical infarction volume (FK506 vs. vehicle; 30 min: 95 +/- 33 mm3 vs. 170 +/- 62 mm3, p < 0.05; 60 min: 93 +/- 45 mm3, vs. 168 +/- 35 mm3, p < 0.05, respectively). FK506 was ineffective when given at 120 min after ischemia. FK506 had no effect on edema formation, nor on the infarct volume in striatum. The therapeutic time window for this low dose of FK506 given i.v. is between 60 and 120 min in this model.

Ice storm damage and early recovery in an old-growth forest.

We quantified the damage caused by a major ice storm to individual trees in two 1-ha permanent plots located at Mont St. Hilaire in southwestern Québec, Canada. The storm, which occurred in January 1998, is the worst on record in eastern North America; glaze ice on the order of 80-100 mm accumulated at our study site. All but 3% of the trees (DBH > or = 10 cm) lost at least some crown branches, and 35% lost more than half their crown. Damage to trees increased in the order: Tsuga canadensis, Betula alleghaniensis, Ostrya virginiana, Acer saccharum, Fagus grandifolia, Quercus rubra, Betula papyrifera, Acer rubrum, Tilia americana, and Fraxinus americana. Only 22% of the saplings and small trees (4 cm < DBH < 10 cm) escaped being broken or pinned to the ground by falling material. Levels of damage generally were greater in an exposed ridge top forest than in a cove protected from wind. By August 1999 only 53% of the trees had new shoots developing from the trunk or broken branches; among the more dominant canopy trees, Fagus grandifolia had the least sprouting and Acer saccharum and Quercus rubra the most. We anticipate and will monitor both significant turnover in the tree community and some shift in composition of the canopy dominants.

[Efficacy of lidocaine cream in protecting against thermal stress during hyperthermia].

Hyperthermia is performed in combination with chemotherapy as multimodal treatment for recurrent and advanced cancer. It is generally believed that the temperature cannot be raised higher because of thermal stress. In this study, we examined the efficacy of lidocaine cream in protecting against thermal stress during hyperthermia. We devised a new local anesthetic cream containing 5% lidocaine. The subjects were eighteen patients with stomach cancer, liver cancer, or large intestine cancer. This cream was applied locally to the skin with an occlusive dressing for about one hour before hyperthermia was performed, and was wiped away just before hyperthermia. The pain scores in the treatment group were significantly lower than in the no-treatment group (p < 0.05). The scores for sensation of heat in the treatment group were lower, though not to a significant extent, than those in the no-treatment group. No adverse effects were observed. Plasma concentrations of lidocaine were lower than 0.5 microgram/ml, and percutaneous absorption of lidocaine from the lidocaine cream was minimal.

Neutrophil functions and cytokine production in patients with gastric cancer.

BACKGROUND/AIMS: One of the most important factors in the prevention of postoperative infection is the patient's own capacity to protect against infection. Neutrophils play a major role in this protection through phagocytosis and superoxide generation. Inflammatory cytokines are suitable for estimating the degree of surgical stress. The present study was designed to elucidate whether neutrophil functions are impaired in gastric cancer patients, and are related with cytokine production after surgery. METHODOLOGY: Phagocytosis and superoxide generation by neutrophils was studied in 84 patients with gastric cancer by flow cytometry. IL-6, IL-8 and tumor necrosis factor alpha were studied in 18 patients with gastric cancer by enzyme-linked immunosolubent assay. RESULTS: In gastric cancer patients phagocytosis was not impaired, whereas superoxide generation was lower than benign diseases and it was inhibited relative to the clinical stage. Moreover, superoxide generation was correlated with the nutritional parameters and was more suppressed in 7 patients who suffered from postoperative infection than in 40 patients whose postoperative course were uneventful. The fluctuation of superoxide generation correlated well with the serum cytokine levels in the postoperative course and its correlation was clarified in vitro. Nine patients with gastric cancer received intravenous hyperalimentation, and their superoxide generation was increased. CONCLUSIONS: Superoxide generation by neutrophils was suppressed in gastric cancer patients and it is suggested that nutritional support prevents postoperative infection via the augmentation of superoxide generation.

Preparation of fine emulsified fat particles without glycerol for intravenous nutrition.

A method of preparing fine emulsified fat particles without glycerol for intravenous nutrition was investigated. The factors assessed were the oil phase ratio, the glucose level of the aqueous phase and the temperature of high-pressure homogenization. The particle size decreased with an increase in the oil phase ratio and it went below 250 nm only in the emulsion with a 50% oil phase ratio. The weight-weighted particle size (dw)/number-weighted particle size (dn) value reflected the particle size distribution. The emulsion with a 50% oil phase ratio had a very narrow distribution of particle sizes and the dw/dn value was below 1.1. With the use of glucose solutions for the aqueous phase, smaller particle sizes and narrower distributions were obtained with increasing glucose concentrations. The controlled temperature of 50 degrees C was appropriate for high-pressure homogenization, producing particles below 160 nm. The rate of the layer separation was a function of particle size. The particle sizes below 180 nm can be expected to suppress the separation of the formulation which consisted of 10.0% soybean oil, 1.2% phospholipids and 5.0% glucose. The stability studies were conducted at 40 degrees C for 3 months and the fat emulsion was stable during storage. These investigations contribute to the preparation of a new caloric source for peripheral parenteral nutrition.

Degradation kinetics of L-glutamine in aqueous solution.

The degradation kinetics of L-glutamine (Gln) in aqueous solution was studied as a function of buffer concentration, pH and temperature. Stability tests were performed using a stability-indicating high-performance liquid chromatographic assay. The degradation product of Gln was 5-pyrrolidone-2-carboxylic acid. The reaction order for Gln in aqueous solution followed pseudo-first-order kinetics under all experimental conditions. The maximum stability of Gln was observed in the pH range from 5.0 to 7. 5. The pH-rate profile described by specific acid-base catalysis and hydrolysis by water molecules agreed with the experimental results. Arrhenius plots showed the temperature dependence of Gln degradation, and the apparent activation energy at pH 6.41 was determined to be 9.87 x 10(4) J mol(-1).

P-glycoprotein-expressing tumor cells are resistant to anticancer drugs in human gastrointestinal cancer.

The resistance to doxorubicin (DOX) by some tumor cells is mainly due to the effect of P-glycoprotein encoded by the multidrug resistance-1 (mdr1) gene. We tried to prove the correlations between P-glycoprotein expression and the sensitivity for anticancer drugs including DOX and other cytotoxic drugs that are currently used for gastrointestinal cancer patients. We quantified the P-glycoprotein expression by flow cytometry techniques, and the sensitivity for anticancer drugs using a tetrazolium salt, 3-(4,5-di-methylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), assay in highly purified fresh human tumor cells obtained from 25 cancer patients. The inhibition rates were the lowest in DOX and mitomycin C (MMC), compared with other drugs. The most significant correlation between DOX and MMC was seen in the inhibition rates. A significant correlation was also seen between the inhibition rates for DOX and P-glycoprotein expression, whereas only a slight correlation between the sensitivity for MMC and P-glycoprotein expression was observed. We should therefore pay close attention to the effect of P-glycoprotein when treating cancer patients, especially if both the inhibition rates of DOX and MMC are low based on the findings of an MTT assay.

P-glycoprotein expression and chemosensitivity in highly purified fresh human gastrointestinal cancer cells.

BACKGROUND/AIMS: Colorectal cancer is one of the tumors most refractory to treatment by chemotherapy. One of the major problems associated with cancer chemotherapy is drug-resistance of tumor cells, and resistance to doxorubicin (DOX) is mainly due to the effect of P-glycoprotein. We have tried to prove the correlation between P-glycoprotein expression and DOX-sensitivity in highly purified fresh human colorectal cancer and, moreover, to prove the differentiation of P-glycoprotein expression between the different kinds of cancers, including gastric cancer. METHODOLOGY: The present study was designed to quantify P-glycoprotein expression by flow cytometry, and DOX-sensitivity by MTT assay in highly purified fresh human tumor cells obtained from 29 cancer patients including 13 colorectal cancers and 16 gastric cancers. RESULTS: DOX-sensitivity decreased in proportion to P-glycoprotein expression in colorectal cancer. P-glycoprotein expression in colorectal cancer was higher than that in gastric cancer. Particularly, P-glycoprotein expression in colorectal cancer in the DOX low-sensitivity group was higher than in the DOX high-sensitivity group. CONCLUSIONS: The chemotherapeutic management of patients with colorectal cancer might be more effective if we can circumvent the effect of P-glycoprotein.

Degradation kinetics of L-alanyl-L-glutamine and its derivatives in aqueous solution.

The degradation kinetics of five glutamine dipeptides in aqueous solution, i.e. glycyl-L-glutamine (Gly-Gln), L-alanyl-L-glutamine (Ala-Gln), L-valyl-L-glutamine (Val-Gln), L-leucyl-L-glutamine (Leu-Gln) and L-isoleucyl-L-glutamine (Ile-Gln), were studied. Stability tests were performed using a stability-indicating high-performance liquid chromatographic assay. Two different Ala-Gln degradation routes, i.e. the cleavage of a peptide bond and the deamination of an amide group, were observed. The degradation was adequately described by pseudo-first-order kinetics. The maximum stability of Ala-Gln was obtained at an approximate pH of 6.0. The pH-rate profile described by specific acid-base catalysis and hydrolysis by water molecules agreed with the experimental results. The activation energy of Ala-Gln at pH 6.0 was determined to be 27. 1kcal mol-1, and the shelf-life (90% remaining) at 25 and 40 degrees C was predicted to be 5.3 years and 7.1 months, respectively. The rate constants of the glutamine dipeptides were influenced by the N-terminal amino acid residue and decreased in the order: Gly-Gln, Ala-Gln, Leu-Gln, Val-Gln and Ile-Gln.

Comparison of glucose and fat as energy sources in peripheral parenteral nutrition in rats.

Glucose is usually chosen as the energy source for total parenteral nutrition. However, the optimal glucose:fat ratio for peripheral parenteral nutrition has not been examined sufficiently. We compared glucose:fat ratios in hypocaloric nutrition. Male SD rats were given hypocaloric parenteral nutrition (approx. 190 kcal/kg/d) for 5 d after laparotomy. The hypocaloric solutions used contained 0, 33, 50, 67 or 100% of the non-protein energy in the form of fat. Body weight change, nitrogen balance, organ weights, and hepatic, splenic and plasma biochemistries were assessed. Body weight increase in the 67 and 100% fat groups was significantly greater than that in the 0% fat group. Nitrogen balance was the same in all groups. Hepatic glycogen content was significantly lower in the 100% fat group than that in the 0% fat group. The weight of epididymal fat deposits was significantly lower in the 0% fat group than in the 50 and 67% fat groups. On the other hand, tissue triglyceride content and plasma lipid levels in the 100% fat group were significantly higher than in the 0% fat group, and were also higher than in the control group. It is suggested that combinations of glucose and fat have sparing effects on body fat and hepatic glycogen. Combinations of glucose and fat as non-protein energy sources were superior to glucose or fat alone for hypocaloric parenteral nutrition.

Serum paraoxonase activity and its relationship to diabetic complications in patients with non-insulin-dependent diabetes mellitus.

Paraoxonase (PON) is an esterase associated with high-density lipoprotein (HDL). Serum PON activity is affected by PON gene polymorphism (L/M, Leu-Met54, and Q/R, Gln-Arg191). We investigated PON activity and polymorphism in 108 patients (53 men and 55 women) with non-insulin-dependent diabetes mellitus (NIDDM) and 161 control subjects (82 men and 79 women) matched to the patients by age and gender. Serum PON activity was determined using paraoxon as a substrate. PON gene polymorphisms were detected by the restriction fragment length polymorphism method after a polymerase chain reaction. The mean PON activity in the patients was significantly lower than in the controls (116+/-55 and 162+/-57 U/L, respectively, P < .001). The distribution of each genotype showed no difference between the patient and control groups, and PON activity increased in the order of the QQ < OR < RR genotype and MM < LM < LL genotype in both groups. However, among each genotype subgroup, the activity was lower in patients than in controls. Forty-one patients with retinopathy had lower PON activity than those without the complication (94+/-36 and 129+/-61 U/L, respectively, P < .002). There was also a significant difference in PON activity between patients with and without overt proteinuria (93+/-38 and 122+/-58 U/L, respectively, P < .05). Logistic analysis showed that serum PON activity was one of the significant factors for retinopathy. These results suggest that decreased PON activity in patients with NIDDM is involved in diabetic vascular complications.

Lobular form idiopathic glomerulonephritis with massive subendothelial and paramesangial immune deposits, a three-year follow-up case.

We report a patient with unusual glomerulonephritis. A 24-year-old Japanese female was hospitalized in October 1995 because of nephrotic syndrome. Lobular form glomerulonephritis with mesangial proliferation associated with massive wide-spread accumulation of slightly eosinophilic, periodic acid Schiff-positive amorphous materials in the luminal side of the capillary walls and paramesangial area was observed in the renal biopsy specimen. Immunofluorescent study revealed massive strong staining for IgM and C4 along the capillary walls and in the mesangium. Deposits of IgA, IgG, C3 and fibrinogen were also observed. Electron microscopy showed normal thickness of the capillary basement membrane and a large amount of subendothelial and paramesangial electron dense, finely granular deposits without fibrils or tubular structures. There were no clinical or laboratory findings of systemic diseases, such as systemic lupus erythematosus and cryoglobulinemia. Therefore, we believed that this case involved an unusual idiopathic glomerular disease with massive subendothelial and paramesangial immune deposits. Glomerulonephritis in this patient appeared to be resistant to treatment with corticosteroids and that this glomerulopathy may be a progressive disease as shown during the 3-year observation. Furthermore, our patient had idiopathic hyperprolactinemia and subclinical hypothyroidism. However, the relationship between glomerulonephritis and endocrinopathy in our patient is unknown.